登录
 机构网站
  1. 首页
  2. 情报产品
  3. 快讯详情

《BioRxiv，1月31日，The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangzx
  • 发布时间：2020-02-01

  • The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells

    Markus Hoffmann, Hannah Kleine-Weber, Nadine Krueger, Marcel A Mueller, Christian Drosten, Stefan Poehlmann

    doi: https://doi.org/10.1101/2020.01.31.929042

    Abstract

    The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum from a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention.

  • 原文来源：https://www.biorxiv.org/content/10.1101/2020.01.31.929042v1
11浏览量
原文链接
相关报告

  • 《BioRxiv，2月21日，Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-02-22
    • Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV) Jiahua He, Huanyu Tao, Yumeng Yan, Sheng-You Huang, Yi Xiao doi: https://doi.org/10.1101/2020.02.17.952903 Abstract Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019- nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV. *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.
    83浏览量
    原文链接

  • 《bioRxiv，2月21日，A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-02-22
    • A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells Zhaoqian Su, Yinghao Wu doi: https://doi.org/10.1101/2020.02.20.958272 Abstract The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensin-converting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS. *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.
    10浏览量
    原文链接